SHOOTING THE VECTOR: NEW TECHNOLOGIES AND THEIR USES TO SUPPRESS A DEADLY ANIMAL

By Tessa Smith, 7th October 11:30 AM

Like all good netizens, I have at least once gotten into an argument with strangers on the internet.  The argument in question was about whether it was ‘ethical to purposely drive a species (in this case, a mosquito) to extinction’. I argued that it was not ethical, on the basis that the species has the same inherent right to survive as all other species, including the charismatic ones. The other parties (for there were many) argued that I was a privileged idiot with no empathy for the millions of people worldwide affected by the diseases. They probably had a point, but ethics aside, it got me thinking about 1) what the problem with the mosquito was, 2) what was being developed to supress it, and 3) how likely it was that the species could become extinct as a result. Thanks to Emily Flies for her helpful suggestions to the piece.


1. The Problem

According to the World Health Organisation, mosquito-borne diseases cause several million deaths and hundreds of millions of infections each year. Mosquitoes of the genus Aedes, Anopheles and Culex are the primary culprits for transmission of infections (e.g. malaria, Ross River virus). In these genera, the female mosquito feeds on blood from a host, using the protein and iron in the blood to grow her eggs. By feeding on several hosts (from the same or different species), they may transmit the blood-borne diseases if present.

A.aegypti

Figure 1: Aedes aegypti mosquito, E. A. Goeldi (1905).

Aedes aegypti (Figure 1), which is a vector for multiple diseases and lives in urban areas, thereby threatening over half of the world’s population. They are one of the most important species for transmitting disease for two main reasons: 1) they feed during the day (from sunrise to after sunset) when people are outdoors and active, giving them more opportunities to infect people, and 2) they lay their eggs in small containers of water around urban areas, making it very hard to target control efforts to breeding sites. While not the only insect vector for the multiple diseases it can spread, A. aegpyti is by far the most common and of the most concern. Some of the diseases transmitted by Aedes aegypti are:

  • Yellow fever is endemic in Africa and South America where its primary reservoir is monkeys. The disease can cause death in a small percentage of infected people and there is a vaccine available. During 2017-2018 there were deadly outbreaks of the disease in Brazil and Nigeria.
  • The Zika virus has been recorded in over 86 countries in the Americas, Africa, Asia and the Pacific. While causing few symptoms from infection in most people, it can cause complications of pregnancy and malformation in babies. Those infected also suffer an increase risk of neuropathic conditions. There is no vaccine currently available for Zika.
  • Chikungunya is present in Africa, Asia, the Americas and Europe. It causes fever and joint pain in affected individuals and there is currently no vaccine for the disease.
  • Dengue is most prevalent in Asia, the Americas and Africa, with almost half of the world’s population at risk (Figure 2). The disease may have been underreported in Africa due to a range of factors including presence of similar illnesses (11). The disease disproportionately affects people in developing countries (especially indigenous people, people of colour and immigrants) (10).There is currently no vaccine for Dengue, and the vaccine discovery process proving difficult. Aedes mosquitos are not a vector for malaria.

Fig2

Figure 2: World Health Organization Estimated Deaths from Dengue per million persons, 2012. Yellow=0, Red=9 (CC BY-SA 4.0).

Here, I focus on the research aimed at suppressing the ability of this species to transmit disease.

The spread of Aedes aegypti away from its native home in Africa and to a large area of the world, especially tropical and subtropical areas is also a major concern. The distribution of the mosquito in some areas of South America has been attributed to ship dispersal during the slave trade in the 1600’s (13) and more recently the trade in used car tyres (WHO Dengue Control). 

Controlling the spread and reproduction of these mosquitoes is critical for reducing disease transmission. A variety of historical control methods have been used against Aedes mosquitos, some of which have caused widespread environmental problems:

a) The mosquito was nearly eradicated in the Americas in the 1960’s using DDT (the chemical Dichlorodiphenyltrichloroethane), but re-established itself there when the project was discontinued (7) due to strong health and environmental concerns.

b) Biological control of the mosquito with fish or predatory copepods has had limited local success in controlling mosquito numbers and has caused ecological problems when the exotic species escape and consume indigenous fauna. The mosquito fish (Gambusia holbrooki) was listed as one of the IUCN’s 100 most harmful invasive exotic species after being released around the world to eat mosquito larvae.

The challenge of combatting the spread of mosquitoes is also influenced by other factors. The cost of effective management programs using insecticides is ongoing, and often a burden for poorer governments. Many mosquito species are evolving insecticide resistance, making insecticides increasingly ineffective. With climate change there is a predicted increase in A. aegypti’s global distribution (Figure 3) as it establishes in areas that were previously too cold to inhabit (3).

Fig3

Figure 3: Summary of the modelled global distribution of Aedes aegypti under both current (dark blue) and future (dark orange) climatic conditions in 2050 showing stability of predictions at present and into the future with RCP (representative concentration pathway) 4.5 (3).

Traditional methods of controlling Aedes and its disease spread through chemical and biological control are increasingly inneffective and unsustainable, necessitating the use of new methods for control (4). 

2. New options in the control of mosquito-borne disease

Wolbachia bacteria

Wolbachia is a genera of bacteria that occur naturally in 60% of all insect and nematode species, including some mosquitos. The bacterium modifies the sperm of the host insect, only allowing eggs infected with Wolbachia to develop normally (8). The presence of the bacteria within the mosquito has also been found to reduce the ability of the mosquito to transmit Dengue virus to humans.  

fig4

Figure 4: The Percentage of mosquitos with Wolbachia, Townsville, Australia, 2015-2016 (6).

The introduction of the Wolbachia bacteria into A.aegypti mosquitos has been successful in local trials in northern Australia since 2011 (Eliminatedengue.com). Once introduced, Wolbachia is self sustaining within the local mosquito population (Figure 4). Modelling by Dorigatti, McCormack (4) predicted that infection with Wolbachia reduces a mosquito’s ability to transmit dengue by 40% .

Genetic modification and gene drive

Another method for reducing infection rates is the release of genetically modified Aedes into the wild population. Unlike normal inheritance where an altered gene is not always spread, with gene drive inheritance, the altered gene is always inherited; male mosquitos carry a dominant lethal gene, that is passed on when they mate with females and kills 96% of their progeny (12). Modified Aedes aegypti mosquitos have so far been released into Burkina Faso and Brazil where they have been able to suppress local populations (4). This process requires the release of many modified mosquitos over several months (9).

Non-gene drive genetically modified mosquitos released in Brazil were found to have passed portions of their DNA into local populations, forming viable hybrid individuals that bred to pre-release numbers within months (2). The establishment of a genetic monitoring program (2) was recommended as an important part of the development process for any new genetic tool to ensure success.

3. How likely is it that the mosquito will become extinct as a result?

In a laboratory population, gene drive was successfully used to eliminate a population of Anopheles gambiae mosquitoes (a species that spreads Malaria)(5). The likelihood of gene drive and Wolbachia to create a complete extinction of the Aedes aegypti species over their entire range is low, but possible; models suggests that non-random mating will likely prevent gene-drives from causing extinction (1). However, this may be investigated by future research teams.  

All posts are personal reflections of the blog-post author and do not necessarily reflect the views of all other DEEP members.

References:

  1. Bull J. J., Remien C. H., Krone S. M. Gene-drive-mediated extinction is thwarted by population structure and evolution of sib mating. Evolution, Medicine, and Public Health. 2019; 2019(1): 66-81.
  2. Evans B. R., Kotsakiozi P., Costa-da-Silva A. L., Ioshino R. S., Garziera L., Pedrosa M. C., Malavasi A., Virginio J. F., Capurro M. L., Powell J. R. Transgenic Aedes aegypti Mosquitoes Transfer Genes into a Natural Population. Scientific Reports. 2019; 9(1): 13047.
  3. Kamal M., Kenawy M. A., Rady M. H., Khaled A. S., Samy A. M. Mapping the global potential distributions of two arboviral vectors Aedes aegypti and Ae. albopictus under changing climate. PloS one. 2019; 13(12): e0210122.
  4. Dorigatti I., McCormack C., Nedjati-Gilani G., Ferguson N. M. Using Wolbachia for Dengue Control: Insights from Modelling. Trends in parasitology. 2018; 34(2): 102-113.
  5. Kyrou K., Hammond A. M., Galizi R., Kranjc N., Burt A., Beaghton A. K., Nolan T., Crisanti A. A CRISPR–Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes. Nature Biotechnology. 2018; 36: 1062.
  6. O’Neill S., Ryan P., Turley A., Wilson G., Retzki K., Iturbe-Ormaetxe I., Dong Y., Kenny N., Paton C., Ritchie S., Brown-Kenyon J., Stanford D., Wittmeier N., Anders K., Simmons C. Scaled deployment of Wolbachia to protect the community from Aedes transmitted arboviruses [version 1; peer review: 1 approved, 1 approved with reservations]. Gates Open Research. 2018; 2(36).
  7. Hotez P. J. Zika in the United States of America and a Fateful 1969 Decision. PLOS Neglected Tropical Diseases. 2016; 10(5): e0004765.
  8. Jiggins F. M. Open questions: how does Wolbachia do what it does? BMC Biology. 2016; 14(1): 92-92.
  9. Carvalho D. O., McKemey A. R., Garziera L., Lacroix R., Donnelly C. A., Alphey L., Malavasi A., Capurro M. L. Suppression of a Field Population of Aedes aegypti in Brazil by Sustained Release of Transgenic Male Mosquitoes. PLoS neglected tropical diseases. 2015; 9(7): e0003864-e0003864.
  10. Hunter P. Tropical diseases and the poor: Neglected tropical diseases are a public health problem for developing and developed countries alike. EMBO reports. 2014; 15(4): 347-350.
  11. Bhatt S., Gething P. W., Brady O. J., Messina J. P., Farlow A. W., Moyes C. L., Drake J. M., Brownstein J. S., Hoen A. G., Sankoh O., Myers M. F., George D. B., Jaenisch T., Wint G. R. W., Simmons C. P., Scott T. W., Farrar J. J., Hay S. I. The global distribution and burden of dengue. Nature. 2013; 496: 504.
  12. Phuc H. K., Andreasen M. H., Burton R. S., Vass C., Epton M. J., Pape G., Fu G., Condon K. C., Scaife S., Donnelly C. A., Coleman P. G., White-Cooper H., Alphey L. Late-acting dominant lethal genetic systems and mosquito control. BMC Biology. 2007; 5(1): 11.
  13. Mousson L., Dauga C., Garrigues T., Schaffner F., Vazeille M., Failloux A.-B. Phylogeography of Aedes (Stegomyia) aegypti (L.) and Aedes (Stegomyia) albopictus (Skuse) (Diptera: Culicidae) based on mitochondrial DNA variations. Genetical Research. 2005; 86(1): 1-11.

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